Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
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- dc.contributor.author Saiz, Néstor
- dc.contributor.author Mora Bitria, Laura
- dc.contributor.author Rahman, Shahadat
- dc.contributor.author George, Hannah
- dc.contributor.author Herder, Jeremy P.
- dc.contributor.author García Ojalvo, Jordi
- dc.contributor.author Hadjantonakis, Anna-Katerina
- dc.date.accessioned 2020-10-07T05:49:50Z
- dc.date.available 2020-10-07T05:49:50Z
- dc.date.issued 2020
- dc.description.abstract Precise control and maintenance of population size is fundamental for organismal development and homeostasis. The three cell types of the mammalian blastocyst are generated in precise proportions over a short time, suggesting a mechanism to ensure a reproducible outcome. We developed a minimal mathematical model demonstrating growth factor signaling is sufficient to guarantee this robustness and which anticipates an embryo's response to perturbations in lineage composition. Addition of lineage-restricted cells both in vivo and in silico, causes a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biases the specification of progenitors toward the targeted cell type. Finally, FGF4 couples fate decisions to lineage composition through changes in local growth factor concentration, providing a basis for the regulative abilities of the early mammalian embryo whereby fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.
- dc.format.mimetype application/pdf
- dc.identifier.citation Saiz N, Mora-Bitria L, Rahman S, George H, Herder JP, Garcia-Ojalvo J, Hadjantonakis AK. Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development. Elife. 2020; 9:e56079. DOI: 10.7554/eLife.56079
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.56079
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/45407
- dc.language.iso eng
- dc.publisher eLife
- dc.relation.ispartof Elife. 2020; 9:e56079
- dc.rights © 2020, Saiz et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Blastocyst
- dc.subject.keyword Cell fate
- dc.subject.keyword Cell numbers
- dc.subject.keyword Developmental biology
- dc.subject.keyword Imaging
- dc.subject.keyword Modeling
- dc.subject.keyword Mouse
- dc.subject.keyword Mouse embryo
- dc.title Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion